Gamma-nitroalkyl-alpha,beta-dichloro-gamma-crotonolactones



Patented Apr. 1, 1952 GAMMA NITROALKYL ALPHA,BETA DI-CHLORO-GAMMA-CROTONOLACTONES David T. Mowry, Dayton, Ohio, assignor toMonsantoChemical Company, St. Louis, Mo., a corporation of Delaware NoDrawing. Application uly 26, 1950, Serial No. 176,083

16 Claims.

. 1 This invention relates to lactones and deals more particularly withnew derivatives of certain crotonolactones, to a method of preparing thesame, and to biological toxicants comprising new vidual catalystemployed.

sodium, potassium, lithium, calcium or magnesium hydroxide; basicallyreacting salts such as compounds herein disclosed. 5 sodium carbonate,sodium bicarbonate, potassium The new lactones, which I have found topossess. acetate; alkali or alkali metal alcoholates such as highfungicidal, bactericidal and herbicidal efiisodium methylate; organicbases such as pyridine, ciency, have the general formula piperidine,triethylamine, etc.

The mixture of mucochloric acid, nitroparaflin and alkaline condensingagent, in the presence or absence of an inert diluent, is generallyallowed 01- -c-n to stand for a time of, say, from a few minutes toseveral hours depending upon the nature of the nitroparafiin andcatalyst and the temperature employed, and the nitroalkyl dichloro cromwhich R1 and R2 are members of the 0195s tonolactone is separated fromthe reaction prodconsisting of hydrogen and alkyl radicals of from t, gby precipitation fr m a non-solvent such one to 5 carbon atoms and inwhich the sum as water, by vacuum distillation, etc. For good total ofcarbon atoms in 1 and 2 does not yields of the lactone, I find itadvantageous to exceed 6- s u tr t v f c p u ds a n acidify the reactionproduct before the separatthe above general formula m y be mentioned ingstep. The acidifying may be conveniently 'v- Y 'y-( 'Y- combined withthe separating step by treating the D D y 'Y- 11 y 'Y-( -n D Dy Y'reaction mass with aqueous acid. For example, (2-dimethyl-l-nitro t y'ythe crude reaction product may be poured into a th l) r v-(5- it amyB-di -vcold, aqueous solution of a mineral acid such, o o a to e. h y ree di y t e y the as hydrochloric acid, an organic acid such as reaotlonof muooohlono d with a nitropareflin acetic acid, or an acid-reactingsalt such as zinc of r 1 to 6 carbon atoms and possessing a chloride,and the lactone thus precipitated rehydrogen atom on the carbon atom towhich the red by filtration. nitro radical is attached, substantiallyaccording 3O Inasmuch as molecular equivalents of muggto the scheme:chloric acid and the nitroparaflin are involved in R1 01 o o= theformation of the present lactones, it is ad- I vantageous to employstoichiometric proportions c1- COOH of the two reactants. If desired,however, an excess of either reactant may be employed, since R J-R, anyunreactedmaterial may be separated from No: the product. Insomevinstances an excess of the in which R1 and R2 are as defined above.mmn may advantageously be used as a Nltropaltaffin which may be employedwith 40 Although I find that generally no extraneous mucochlonc 3prepamnon the pres solvents or diluents need be employed in the refllactones m1ude mtrmethane' mtroethane, action, inert solvents ordiluents may be used and l-n tropropane, z-mtropropane, 2-mtr0but are ofparticular advantage when working with zmtropentanel and f some of thecatalysts. With the alkali metal hy- The Present vifii -v' droxides, forexample, water or an alcohol is tonolactones are formed by contactingmuco' preferably used to provide a homogeneous reac- Fhlonc acld Wlththe 'P nitropalamni tion medium. While .I prefer to use as a catalyst nthepr s f a a a condensing t. a material which is soluble in either thereactants a Ordinary increased temperaturesw or in the diluent,solubility of the catalyst in any 111 Order to avoid Side reactions, forexample of these materials is not a necessary property of dehalogenationor degradation of the mucochloric the catalyst. acid by the alkalinecatalyst, I generally prefer The present lactones are stable, ratherhighto operate at low or moderate temperatures, say, melting crystallinesolids which may be advanat temperatures of from minus 10 C. to plustageously employed in the chemical and allied 50 0., depending upon thenature of the indi- 56 industries for a wide variety of purposes. Theyare of general utility asbiological toxicants, par-i 150 cc. ofconcentrated hydrochloric acid.

Per Cent 31.8

ticularly as fungicides, bactericides and herbicides; but some of thisseries of compounds may also be advantageously employed in theformulation of perfumes, as plasticizers or copolymerizable monomers inthe synthetic resins and plastics industries, etc.

The invention is further illustrated, but not limited, by the followingexamples:

Example A solution of 84 g. (0.5 mole) of mucochloric acid and 41 g.(0.55 mole) of nitroethane, dissolved in 200 cc. of methanol, was cooledto 0 0., and 40 g. of sodium hydroxide in 200 cc. of water was slowlyadded to the solution at a temperature of from 0 C. to C. After standingfor 1.5 hours at a temperature of C., the reaction mixture was pouredinto a mixture of ice and A bright blue color developed, and aprecipitate formed on standing. The precipitate was filtered off andrecrystallized from dilute methanol to give the substantially pure'y-(l-nitroethyb- 11,;8-dichloro-' -crotonolactone, M. P. 121 to 122 C.,and analyzing as follows:

Caled. for O H=O ChN Found Per Cent H: 2.23

Per Cent N: 6. 20

The 'y-(1nitroethyl)-c,B-dichlor0lactone was tested against Aspergillusniger using the following testing procedure:

Preliminary.Trommels Malt Agar was poured into a Petri plate and allowedto harden. A circular section was cut from the center and into this cupwas placed 0.1 gram of the lactone. The plate was then sprayed with afresh aqueous spore suspension of Aspergillus niger and incubated at atemperature of 28 C. for five days. Inspection of the incubated plate atthe end of that time showed no growth of Aspergillus niger within a 5mm. zone.

Secondary.To 100 cc. of hot Trommels Malt Agar was added 0.1 gram of thelactone. The agar was then whipped into an emulsion and poured into acold plate and allowed to harden. 50 cc. of hot agar was added to 50 cc.of the above toxic agar to give a lactone concentration of 0.05 percent. To 10 cc. of the remaining toxic agar was added 90 cc. of agar togive a concentration of 0.005 per cent. Petri dishes were filled fromeach of the two mixtures, i. e., that having a lactone concentration of0.05 per cent and that having an 0.005 per cent concentration. Theplates were then sprayed with Aspergillus niger and incubated at atemperature of 28 C. for five days. At the end of that time inspectionof the plates showed that on plates of both the 0.05 per cent and 0.005per cent concentration the growth of Aspergillus niger was completelyinhibited.

Petri plate tests of the lactone against Pythium, conductedsubstantially according to the above procedure, showed no growth of theorganism at a lactone concentration of 5 parts per million.

In tests made on spores of the fungus Sclerotima. fructiola, 100 partsof 'y-(l-nitroethyh- (1.0-dichloro-' -crotonolactone per million partsof water gave a 100 per cent kill of the fungus.

The bactericidal effect of y--(lnitroethyl)- termining the phenolcoeflicient against Staphy- .sodium hydroxide in 50 cc. of water.

4 Zococcus aureus at 20 (3., using the Federal Drug Administrationprocedure. The standard phenol coefficient of the lactone was therebyestablished as greater than 83.

The herbicidal activity of -(l-nitroethyD- a,p-dichloro-'-crotonolactone was determined by germination of cucumber seeds for 4days at a temperature of 76 F. in the presence of aqueous suspensions ofthe chemical at concentrations of 100 parts per million and 10 parts permillion respectively. Seventy-five seeds were used for each test. Theresults are expressed as per cent length of the primary roots in thepresence of the chemical compared with the length of the primary rootsof controls which had been germinated in water. The activities of twostandard herbicides as obtained by the same test are in- I cluded forcomparison.

mucochloric acid and 15.2 g. (0.25 mole) of nitromethane in 60 cc. ofmethanol was treated with 22 g. of sodium hydroxide dissolved in 100 cc.of water. Addition of the alkali was done gradually with stirring andcooling, in order to maintain the temperature of the reaction mixture atfrom 5 C. to 10 C. The solution turned yellow and become viscous. It wasallowed to stand for 30 minutes at a temperature of about 10 C. to 15 C.and then was poured into 1.5 moles of dilute hydrochloric acid in ice.

The almost white precipitate of v-nitromethyl- 1,5-dichloro--crotonolactone thus formed was filtered and dried. It was found todecompose sharply at 84 C.

Petri plate tests of this lactone against Pythium, conductedsubstantially according to the fungicidal testing procedure, describedin Example 1, showed no growth of the organism at a lactoneconcentration of parts per million. Toxicity tests against Stemphyliumsarcinoformae showed per cent toxicity at a lactone concentration of 50parts per million parts of water.

Tests of the v-nitromethyl-a,p-dichloro ycrotonolactone against M.tuberculosis showed complete control at a 40 parts per millionconcentration.

. Example 3 A solution of 11.1 g. (0.125 mole) of 2-nitropropane and 21g. (0.125 mole) of mucochloric acid in 30 cc. of methanol was cooled to0 C. To this there was then slowly added, with stirring, and cooling, asolution of 10.5 g. of

The resulting thick yellow solution was then allowed to stand for 2hours at a temperature of from 10 C. to 15 C. At the end of this timethe reaction mixture was poured into a mixture of ice and 60 cc. ofconcentrated hydrochloric acid. The precipitate which formed wasfiltered, dried, and recrystallized from 100 cc. of 50 per cent aqueousmethanol to give white crystals of the substantially pure'y(2-nitropropyl) -a,p-dichlo- :lo-y-crotonolactone, M. P. 92 to 93 C.,and analyzing as follows:

Tests of the 'y-(2-nitropropyl) -a,}9-diCh101O-'Y- crotonolactoneagainst the fungus Aspergillus niger, conducted as described in Example1 showed complete growth inhibition at 0.005per cent concentration.

Bactericidal tests of this lactone against Staphylococcus aureus, usingthe standard Federal Drug Administration procedure as in Example l, gavea phenol coeflicient of greater than 83.

Tests of the 'y-(2-nitropropyl)-2,,B-dichloro- -crotonolactone as aherbicide, conducted as in Example 1, showed only a 4 per cent rootgrowth at a concentration of 100 parts per million.

The present 'y-nitroalkyl-ap-dichloro-'y-crotonolactones are thusgeneral biological toxicants.

As fungicides they are highly efiicient for preventing and retardingfungus growth on textiles, fur, leather, wood, etc. They may be applieddirectly to the material which is to be treated, but because thelactones are efiective in extremely dilute concentrations, it ispreferred to incorporate the present agents with a carrier or diluent.

Fungicidal, bactericidal or herbicidal dusts may be prepared by mixingthe nitroalkyl dichloro lactone with dusting materials such as talc,clay, lime, bentonite, pumice, fullers earth, etc. The present compoundsare soluble in the usual organic solvents; and solutions of the lactonesin such solvents may be used as sprays.

Suspensions or dispersions of the lactones in a non-solvent such aswater are advantageously employed in the treatment of plant foliage,textiles, leather, and other materials with which it is not desirable toemploy either a solid carrier or an organic solvent.

What I claim is:

1. Lactones having the general formula in which R1 and R2 are members ofthe class consisting of hydrogen and alkyl radicals of from 1 to 5carbon atoms and in which the sum total of carbon atoms in R1 and R2does not exceed 6.

2. 'y Nitromethyl a,p-dichloro-v-crotonolactone.

3. l-nitroethyl) -a,p-dichloro-v-crotonolac tone.

4. 'y (2 nitropropyl) -a,;3-diCh101'O'Y-C10tOIlO- lactone.

5. The process which comprises contacting mucochloric acid, in thepresence of a basic condensing agent, with a nitroparaflin having thegeneral formula in which R1 and R2 are members of the class consistingof hydrogen and alkyl radicals of from 1 to 5 carbon atoms and in whichthe sum total of carbon atoms in R1 and R2 does not exceed 6, acidifyingthe resulting mixture, and recovering from the acidified product alactone having the general formula c1-c-c 0 0 c1- C-H Rq--Rfl NO; inwhich R1 and R2 are members of the class consisting of hydrogen andalkyl radicals of from 1 to 5 carbon atoms and in which the sum total ofcarbon atoms in R1 and R2 does not exceed 6.

6. The process which comprises contacting, at low temperatures and inthe presence of an aqueous solution of an alkali metal hydroxide,mucochloric acid with a nitroparaifin having the general formula inwhich R1 and R2 are members of the class consisting of hydrogen andalkyl radicals of from 1 to 5 carbon atoms and in which the sum total ofcarbon atoms in R1 and R2 does not exceed 6, acidifying the resultingmixture, and recovering from the acidified product a lactone having thegeneral formula in which R1 and R2 are members of the class consistingof hydrogen and alkyl radicals of from 1 to 5 carbon atoms and in whichthe sum total of carbon atoms in R1 and R2 does not exceed 6.

7. The process which comprises contacting mucochloric acid withnitroethane at low temperatures and in the presence of an aqueoussolution of an alkali metal hydroxide, acidifying the resulting mixture,and recovering 'y-(1nitroethyl) afi-dichloro-'y-cr0t0nolact0ne from theacidified product.

8. The process which comprises contacting mucochloric acid withnitromethane at low temperatures and in the presence of aqueous alkalimetal, acidifying the resulting mixture and recovering 7 nitromethy1-a,3-dichloro-' -crotonolactone from the acidified product.

9. The process which comprises contacting mucochloric acid withZ-nitropropane at low temperatures and in the presence of aqueous alkalimetal, acidifying the resulting mixture and recovering 'y(Z-nitropropyl) -a,fl-dichloro-'y-crotonolactone from the acidifiedproduct.

10. A. biological toxicant comprising an inert carrier and as an activeingredient, in a quantity which is toxic to living organisms, a lactonehaving the general formula in which R1 and R2 are members of the classconsisting of hydrogen and alkyl radicals of from J,

to carbon atoms and in which the sum total of carbon atoms in R1 and R2does not exceed 6.

11. A fungicidal composition comprising an inert carrier and as theactive ingredient, in a quantity which is toxic to fungi, a lactonehaving the general formula in which R1 and R2 are members of the classconsisting of hydrogen and alkyl radicals of from 1 to 5 carbon atomsand in which the sum total of carbon atoms in R1 and R2 does not exceed6.

13. A herbicidal composition comprising an inert carrier and as theactive ingredient, in a quantity which is suflicient to injure livingplants, a lactone having the general formula GlC-C=O in which R1 and R2are members of the class consisting of hydrogen and alkyl radicals offrom 1 to 5 carbon atoms and in which the sum total of carbon atoms inR1 and'Rz does not exceed 6.

14. A biological toxicant comprising an inert carrier and 'y nitromethylc,B-dichloro-- -crotonolactone, as the active ingredient, said lactonebeing present in a quantity which is toxic to living organisms.

15. A biological toxicant comprising an inert carrier and7-(1-1111310817115'1) -a,/3-di0hlO1O-'y-Cr0 tonolactone, as the activeingredient, said lactone being present in a quantity which is toxic toliving organisms.

16. A biological toxicant comprising an inert carrier and 7-(2-nitropropyl) -a,B-di(3h10IO-'y-c10- tonolactone, as the activeingredient, said lactone being present in a quantity which is toxic toliving organisms.

DAVID T. MOWRY.

REFERENCES CITED UNITED STATES PATENTS Name Date Stand Dec. 24, 1940Number

1. LACTONES HAVING THE GENERAL FORMULA
 2. Y- NITROMETHYL -A,B-DICHLORO-Y-CROTONOLACTONE.